The Legacy of the Philadelphia Chromosome: From Discovery to Therapy: A Symposium in Honor of Peter C. Nowell, MD

On September 13, 2006, colleagues and students of Dr. Peter Nowell came together to celebrate his 50-year-plus career at the University of Pennsylvania School of Medicine with an educational symposium in his honor. An educational seminar seems particularly fitting given Dr. Nowell's longstanding dedication to teaching, as evidenced by the number of current and former "students" in the audience. The day was filled with praise from colleagues for his groundbreaking work with the late David Hungerford in 1960, as well as his continued commitment to the field of pathology and the education of future scientists. The day's presentations focused on areas of research which came about because of Dr. Nowell and David Hungerford's perseverance during a time when their theories were doubted.

Dr. Nowell's career at The University of Pennsylvania began at the School of Medicine in 1948. After completing a pathology residency at Presbyterian Hospital and two years as a pathologist for the Naval Radiological Defense Laboratory in San Francisco, he returned to Penn in 1956. He began studying leukemia cells in the laboratory, and eventually went searching for someone to do chromosomal research on these cells. He was introduced to David Hungerford, a graduate student who wanted to do a thesis on human chromosomes, but was still in need of cells to use for his research. That serendipitous meeting put into motion a chain of scientifically critical events that ultimately led to the discovery of Gleevec, a drug that has changed the lives of thousands of patients with Chronic Myelogenous Leukemia (CML).

The two researchers were experimenting with cells from various types of leukemia when David noticed a smaller-than-normal chromosome 22 on the cancer cells of 2 individuals with CML. With the far less sophisticated techniques of the time, they were unable to tell what happened to the material missing from the chromosome. It would be 1972 before another researcher; Janet Rowley, MD, would discover the missing piece of chromosome number 22 attached to chromosome number 9, thereby identifying the first known chromosomal translocation.

Nowell and Hungerford published an abstract of their research in 1960, describing the abnormality that had been found in 9 out of 10 CML patients they studied. The findings were confirmed by a group in the UK, and the abnormality was subsequently named the Philadelphia Chromosome, for the city in which it was discovered. Nowell and Hungerford had shown that this genetic change was required for the development of CML, and they proposed that all cancers were a result of a critical genetic mutation in a single cell. Others did not agree, however, and the Philadelphia Chromosome was dismissed as an isolated phenomenon, but Dr. Nowell was convinced and continued his research.

In 1972, Dr. Rowley described the (9;22) translocation among several other mutations seen in various types of leukemia, but most researchers still did not buy into the genetic change theory. It would be the early 1980's before techniques allowed researchers to closely examine chromosomal abnormalities and to see the link to other types of leukemia. These discoveries inspired Dr. Brian Druker's clinical trials of Gleevec, which began in 1998. The drug was the first to target a specific protein produced by cancer cells. In this case, the abnormal protein produced by the Philadelphia Chromosome, bcr-abl, was targeted. The drug was shown to be extremely effective in treating CML, inducing remissions in large numbers of patients. The drug was then approved in 72 days, faster than any other in the history of the US Food & Drug Administration.

For his achievements in the field of pathology, Dr. Nowell has received numerous awards, including the Lasker Award for basic medical research and the Gold Headed Can Award given by the American Society for Investigative Pathology. Despite all the accolades and praise for his long and distinguished career, Dr. Nowell remains humble, referring to his discovery as a "serendipitous observation". Although Dr. Nowell is "retiring" from his position, he will stay on as Professor Emeritus, with his office door always open to offer his guidance and wisdom to the researchers of the future.